Consider This Case: An Uncontrolled Diabetic Cat

HISTORY

Sugar was diagnosed with diabetes mellitus 2 years prior to presentation. Initially, her diabetes was moderately controlled on 5 to 6 units of recombinant human protamine zinc insulin (PZI) (40 U/mL; ProZinc, bi-vetmedica.com), but over the year prior to presentation the insulin dose had been progressively increased with no improvement in glycemic control.

In addition to diabetes mellitus, Sugar had concurrent hypertrophic cardiomyopathy and chronic rhinitis, and persistent polyuria, polydipsia, polyphagia, and weakness.

Key Points: Feline Diabetes Mellitus

Diabetes is a disease of insulin deficiency.

Diabetes in cats is most commonly classified as type 2-like diabetes—a disease process in which insufficient insulin production from beta cells takes place in the setting of insulin resistance.

Insulin requirements can be altered by obesity, inflammation, or concurrent endocrine disease, such as hypersomatotropism (acromegaly) or hyperadrenocorticism.

Some refer to a subclass of diabetic cats with secondary diabetes—patients in which diabetes occurs subsequent to (1) another endocrine disease (eg, acromegaly, hyperadrenocorticism) or (2) administration of diabetogenic drugs (eg, glucocorticoids).1

PHYSICAL EXAMINATION

Physical examination revealed a symmetrically muscled cat, weighing 7.7 kg, with a body condition score of 6/9. Sugar had an unkempt hair coat, mild prognathia inferior, and a broad head (Figure 1), and walked with a plantigrade stance (Figure 2). No organomegaly was appreciated, and the cat appeared to have normal mentation.

Urinalysis was unremarkable except for glucosuria (> 1000 mg/dL; reference range, negative); urine culture revealed no growth. A blood glucose curve was performed that showed no response to insulin, and all blood glucose values were between 350 to 400 mg/dL.

Initial Diagnostics

Make sure to take a thorough history and perform a complete physical examination, CBC, serum biochemical profile, fructosamine, urinalysis, and urine culture. In addition, also review insulin administration and handling with the owner.

Perform one or multiple blood glucose curves at home or in hospital to assess response to insulin, insulin dose, and duration of effect. Single blood glucose measurements collected in hospital can help identify hypoglycemia, but should not be used to assess control.

Additional Diagnostics

Additional testing to consider, depending on the physical examination and initial diagnostic findings in each individual patient, includes:

Unusual Concurrent Endocrine Diseases

Evaluate the patient for clinical signs or examination findings consistent with hyperadrenocorticism, such as thin/fragile skin (Figure 3) or pot belly. If hyperadrenocorticism is suspected, the test of choice is a low-dose dexamethasone suppression test, using dexamethasone, 0.1 mg/kg IV.1

Acromegaly is an uncommon cause of insulin resistance in cats. In a poorly regulated diabetic cat, lack of a typical acromegalic appearance (prognathism, enlarged feet) does not negate the importance of testing for this condition by measuring serum levels of IGF-1 and performing advanced imaging of the brain.2

Consider This Disease: Acromegaly

Acromegaly, also known as hypersomatotropism, is a disease characterized by excess GH, which stimulates increased production of IGF-1 in the liver and other tissues. GH and IGF-1 cause a variety of changes in the body, including organ enlargement and increased proliferation of bone that can be seen visually as jaw enlargement (prognathism) or large paws.2,4,5

Profile

Acromegaly and excess GH are typically caused by a pituitary adenoma. GH has anti-insulin effects, causing increased glucose production in the liver and reducing insulin sensitivity in the body by a variety of mechanisms. When insulin resistance and glucose production cause elevation of serum blood glucose, the animal becomes diabetic.

Prevalence of acromegaly in diabetic cats is unknown, but is suspected to be as high as 30% of difficult-to-regulate diabetic cats.4 It is typically seen in elderly male cats.

Diagnostic Approach

In practice, diagnosis of acromegaly is based on:

Common clinical signs, including polyuria, polydipsia, and polyphagia—clinical signs associated with diabetes mellitus—as well as weight gain. Neurologic signs may be seen.

Physical examination findings, including an enlarged liver and kidneys on abdominal palpation. In more advanced disease, prognathia inferior and enlargement of the head and paws may be noted.

IGF-1 levels—considered a sensitive but not specific test.

If values are > 1000 ng/mL (131 nmol/L), acromegaly should be suspected, and additional testing, specifically pituitary imaging, is indicated.

The “gray” zone is considered 800 to 1000 ng/mL.

If acromegaly is suspected, but IGF-1 levels are within reference range (208–443 ng/mL), perform repeat testing in 6 to 8 weeks.

IGF-1 levels can be falsely normal if a cat is in an insulin deficient state.2,4,5

Intracranial imaging, either by CT or magnetic resonance, which documents a pituitary mass and confirms the diagnosis (because IGF-1 levels are not 100% reliable).

Additional Diagnostics

Additional biomarkers are being evaluated, but limited data are available. GH assays are not readily available—blood sampling has to be very specific to prevent degradation of the hormone, and the assay lacks sensitivity and specificity.

Differentiating Diseases

Pituitary-dependent hyperadrenocorticism can also cause severe insulin resistance and a pituitary mass—diagnostic results also seen in diabetic cats with acromegaly. However, clinical presentation of these diseases is often very different:

A computed tomography (CT) scan was performed to evaluate whether a mass was present in the pituitary gland. The CT scan demonstrated a homogenously contrast enhancing mass of the pituitary gland. The pituitary mass was slightly irregular, measuring 0.7 cm in diameter (Figure 4).

These findings confirmed a diagnosis of acromegaly—the cause of the severe insulin resistance and poorly controlled diabetes mellitus.

TREATMENT APPROACH

Ideal treatment for acromegaly has not yet been determined. Current treatment options include radiation therapy, surgery (hypophysectomy), or medical management.

Radiation Therapy

Radiotherapy is the current treatment of choice for pituitary tumors.2,4 Many cats experience improvement or resolution of diabetes mellitus, although other acromegalic signs, such as prognathism and enlarged feet, often persist. However, this treatment modality is expensive and outcomes are not always successful.

Hypophysectomy

Hypophysectomy is the treatment of choice in humans, and may become the treatment of choice in cats. At this time, transsphenoidal hypophysectomy has been performed in acromegalic cats, but is only offered in a few, very specialized veterinary institutions. Although it is a procedure with significant risks, good outcomes have been reported.

Medical Management

Medical management using somatostatin analogues, which inhibit growth hormone (GH) secretion, has been used with some success in humans. However, this medical approach has been evaluated in acromegalic cats, demonstrating little to no effect.2,4

IGF-1 was still elevated at 1262 ng/mL (168 nmol/L), but was significantly reduced from original value.

Contrast CT was repeated and the pituitary mass was decreased in size, measuring 0.3 cm in diameter (Figure 5).

Based on these findings, Sugar’s radiation therapy was determined to be effective. In addition, due to the appearance that her diabetes was controlled, the PZI dose was reduced to 1 unit SC Q 12 H.

Over the next 2 years, Sugar’s PZI insulin dose was further reduced to 0.5 units SC Q 12 H. Her IGF-1 levels were also followed, and continued to decrease to 855 ng/mL (112 nmol/L) and then 672 ng/mL (88 nmol/L).

PROGNOSIS

Prognosis for cats with uncontrolled acromegaly and poorly controlled diabetes mellitus is poor to guarded; without treatment most cats are euthanized within a few months of diagnosis. However, in cats, such as Sugar, in which the concurrent disease causing insulin resistance is recognized and treated appropriately, a favorable outcome is possible since glycemic control often improves.

THIS CASE:OUTCOME

Sugar died of hypertrophic cardiomyopathy 3 years following diagnosis and radiation treatment for acromegaly. A complete necropsy was performed; pertinent findings included pituitary gland multifocal adenomas (Figure 6) and significant pancreatic islet amyloidosis (Figure 7), which is characteristic of feline type 2 diabetes. Prognathism inferior was also noted.

FIGURE 6. Gross pathology image of pituitary adenoma found on necropsy, showing a compressive expansile mass. This patient had hemorrhage within the tumor, which made the mass more apparent on gross pathologic evaluation. Sugar’s mass was difficult to appreciate on gross pathology due to changes from radiation therapy and the fragile nature of the postradiation tissue. Courtesy Dr. Silvia Siso

FIGURE 7. Cross sectional view of Sugar’s pancreas, with significant islet amyloidosis—a characteristic of feline type 2 diabetes. Note it is devoid of endocrine cells and replaced with amphophilic fibrillar material (amyloid). All of Sugar’s islets had this appearance (A). Image of the pancreas in a healthy cat that illustrates normal appearance of an islet of Langerhans, populated with endocrine cells (B). Courtesy Dr. Steven Kubiski

Ann Della Maggiore, DVM, Diplomate ACVIM, is a staff internist at University of California—Davis School of Veterinary Medicine. She received her DVM from University of California—Davis, where she also completed a residency in small animal internal medicine.